This Program Project proposes a coordinated, multidisciplinary program of clinical and basic research by the marrow transplantation unit and collaborating research laboratories and clinical services within Memorial Sloan-Kettering Cancer Center, aimed at elucidating and, where possible, favorably selecting or manipulating the genetic, immunologic, hematopoietic and microenvironmental characteristics of the marrow graft and the host which control or influence the development and adaptation of the hematopoietic and lymphoid progenitor cell populations of the graft within an allogeneic host, as reflected in patients undergoing marrow transplantation for leukemia or lethal congenital disorders of hematopoietic cells. Research and experimental therapeutic progenitors focused on human marrow transplant recipients are specifically oriented to achieve major objectives: (1) Definition of genetically influenced cellular interactions between hematopoietic, lymphoid and stromal constituents of a marrow graft and an allogeneic host which limit or contributes to engraftment, graft vs host disease, and reconstitution of hematopoietic and immunologic function. (2) Evaluation of T-cell depleted marrow transplants, their generation, their engraftment, growth and function, and their potential for GvHD prevention in histocompatible or incompatible primate and human hosts. (3) Development and evaluation of other new approaches to reduce the acute mortality of marrow transplants, specifically: a) CMV human-human hybridoma antibodies for early diagnosis and prevention of CMV infection and b) T cell growth factor (IL-2) as a potentiator of immunologic reconstitution; and (4) development of improved pretransplant cytoreduction regimens to achieve elimination of stromal host marrow elements with reduced toxicity, and to potentiate full engraftment and curative corrections of hematopoiesis in patients with leukemia or lethal congenital blood disorders.